Severe dermatomyositis triggered by interferon beta-1a therapy and associated with enhanced type I interferon signaling.
BACKGROUND
Type I interferons (IFNs) are common therapeutics for several diseases, including viral infections and multiple sclerosis (MS). Although numerous studies have implicated type I INFs with the production of autoantibodies and the development of certain autoimmune disorders, interferon beta has not previously been described in association with dermatomyositis, to our knowledge. Previous microarray studies of muscle biopsy specimens from patients with dermatomyositis disclosed a type I IFN-induced gene expression profile. The central role of plasmacytoid dendritic cell precursors, together with increased type I IFN production, suggests a pivotal role for type I IFNs in dermatomyositis. We report a case of dermatomyositis exacerbated or induced by interferon beta therapy for MS and provide evidence that demonstrates enhanced type I IFN signaling in this patient.


METHODS
We observed new-onset dermatomyositis in a 57-year-old patient treated with interferon beta for MS. His symptoms were exacerbated temporally by interferon beta injections. Immunohistochemical staining of skin biopsy specimens for myxovirus-resistance protein A (a surrogate marker for cutaneous type I IFN signaling) showed increased staining that correlated temporally with interferon beta treatment and subsequent disease activity. In vitro treatment with interferon beta of peripheral blood mononuclear cells isolated from our patient revealed enhanced type I IFN signaling assessed by interferon-induced gene expression profiles.


CONCLUSIONS
To our knowledge, this is the first description of dermatomyositis exacerbated or induced by interferon beta treatment. Our results demonstrate enhanced type I IFN signaling following interferon beta treatment in our patient with dermatomyositis.
Somani
Ally-Khan
AK
Department of Dermatology, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio, USA. somania@ccf.org
Swick
Alan R
AR
Cooper
Kevin D
KD
McCormick
Thomas S
TS
D001707:Biopsy, Needle; D002478:Cells, Cultured; D003882:Dermatomyositis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D007370:Interferon Type I / Q000276:immunology / Q000494:pharmacology*; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000175:diagnosis / Q000188:drug therapy*; D012313:RNA / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D015398:Signal Transduction
D007370:Interferon Type I; D012313:RNA; D016899:Interferon-beta; D000068556:Interferon beta-1a